P962: COMMERCIAL TECLISTAMAB IN ANTI-BCMA THERAPY EXPOSED RELAPSED REFRACTORY MULTIPLE MYELOMA PATIENTS: THE MSKCC EXPERIENCE.
Authors: Ross Firestone, Tala Shekarkhand, Dhwani Patel, Malin Hultcrantz, Alexander Lesokhin, Sham Mailankody, Hani Hassoun, Carlyn Tan, Urvi Shah, Neha Korde, Kylee Maclachlan, Heather Landau, David Chung, Gunjan Shah, Sergio Giralt, Oscar Lahoud, Saad Usmani
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Teclistamab (Tec) is the first CD3 x BCMA bispecific antibody receiving accelerated FDA approval for treatment of relapsed or refractory multiple myeloma (RRMM) in patients who have received ≥4 prior lines of therapy, including a PI, IMiD and an anti-CD38 monoclonal antibody. The approval was based on the results of the MajesTec-1 study (Usmani S et al Lancet 2021, Moreau P et al NEJM 2022), demonstrating a 63% overall response rate in a heavily pretreated RRMM population. Patients with prior exposure to anti-BCMA therapies, such as BCMA targeted ADCs, CAR T-cell products and bispecific antibodies were excluded from this study. Aims: Herein, we present our institutional experience with commercial Tec for RRMM including patients with prior BCMA and GPRC5D directed therapies. Methods: We have performed an IRB-approved, retrospective analysis of clinical outcomes of all patients who have received commercial Tec at MSKCC since its approval on 10/26/2022 using the PCD research database. Descriptive analyses were performed for baseline characteristics. The IMWG criteria (Kumar S et al, Lancet Oncol 2016) were used to assess response and define refractoriness to prior therapies. Immune phenotyping of pre-treatment PBMCs was assessed via high-dimensional flow cytometry using lineage, exhaustion, and activation markers. Serum soluble BCMA levels were assessed using an immunoassay. Results: As of 2/27/2023, 26 patients have received commercial Tec and 18 are response evaluable with ≥1 month of clinical follow-up. Median age was 65 (51-80), prior lines of therapy was 8.5 (4-13), time from diagnosis was 7 years (1.5-16), 44% had high-risk cytogenetics, and 33% had EMD. All patients were triple class refractory and 83% were penta-drug refractory. Twelve had prior anti-BCMA therapy (8 Belamaf, 8 BCMA CART, 1 BCMA bispecifisc, 5 with ≥2 anti-BCMA therapies). Among patients with prior exposure to anti-BCMA therapies, median time from last anti-BCMA therapy was 7.2 months. With a median follow-up time of 2.1 months, the median time to best response was 26 days. Overall response rate was 67% (12/18 pts) in all patients and 55% (6/11 pts) in the prior anti-BCMA therapy group. Pts with ≥2 anti-BCMA therapies had a 40% (2/5) response rate to Tec. Clinical benefit rate (CBR) in all patients was 72% (13/18). Cytokine release syndrome was observed in 8/18 patients (44%) during step-up dosing (5/8 with grade 1 and 3/8 with grade 2 CRS) and CBR was 100% in patients with CRS (88% ORR). Additional notable toxicities include 2 patients with grade 2 neurotoxicity that improved with therapy discontinuation. Summary/Conclusion: To our knowledge, this is the first report of commercial Tec in RRMM. Tec remains effective in relapsed or refractory multiple myeloma despite prior exposure to anti-BCMA therapies, though exposure to multiple prior anti-BCMA therapies may be predictive of diminished efficacy. Clinical data on additional patients will be presented at the meeting. Ongoing translational investigations on soluble BCMA levels and patient-specific immune phenotype will also be presented at the meeting. Keywords: Bispecific, Multiple myeloma, relapsed/refractory